Cell-Based Gene Therapy

To date, over 1800 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical trials from official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our June 2012 update, we have entries on 1843 trials undertaken in 31 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our searchable database are available on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in clinical trials of gene therapy approaches around the world and discuss the prospects for the future.

Viral vector systems are crucial in delivering therapeutic genetic material for gene and cell therapy in clinical settings. With new progress in viral vector-based gene therapies, healthcare professionals and pharmacists must stay informed and apply appropriate biosafety precautions when handling these products. Comprehensive guidelines covering biosafety measures for every viral vector-based gene therapy, including storage, preparation, administration, and disposal, remain scarce. As viral vector-based gene therapy advances rapidly, it is critical to equip healthcare professionals with the expertise to safely manage these agents in a clinical setting. As gene therapies become more integrated into mainstream medicine, with 43 cell and gene therapy products approved as of 2025, pharmacists, nurses, and caregivers face new safety challenges when handling these therapies. While guidelines such as United States Pharmacopeia (USP) 797 and USP 800 provide a foundation for handling viral vector-based gene therapies, no single resource consolidates all biosafety considerations for healthcare professionals. This review provides an overview of the viral vector-based gene therapy landscape. It compiles best practices from various sources to establish a potential standardized approach to guide safe handling procedures for viral vector systems in a healthcare setting. By adopting the biosafety strategies outlined in this article, healthcare staff and pharmacists can safely manage viral vectors while developing standard operating procedures tailored to their specific clinical environments. Implementing these measures will support the continued advancement of gene therapy while ensuring the safety of healthcare providers, patients, and the environment.

The FDA's Regulatory Framework for Chimeric Antigen Receptor-TCell Therapies.

Ischemic stroke is one of the leading causes of death and disability worldwide. There is no effective treatment for ischemic stroke apart from thrombolytic therapy, which has a narrow therapeutic time window. Gene therapy has proven to be effective in experimental stroke, but it suffers from disadvantages that limit its clinical application, such as difficulty in intracranial delivering of therapeutic genes, low efficacy in transfecting host cells and long-term expression of exogenous genes. Delivering therapeutic genes to the ischemic brain via stem cells is an alternative strategy of combined gene and stem cell therapy. There are advantages for stem cell-mediated gene delivery as opposed to direct gene transfer. In recent years, studies used stem cells that over-express different neurotrophic factors, such as BDNF, GDNT, or NT3, and found that the delivery of these genetically-modified stem cells to animal models of ischemic stroke is safe and effective, thus suggesting that stem cell-based gene therapy may be a promising treatment for stroke. This review summarizes the advantages and recent progress of stem cell-based gene therapy for ischemic stroke. We also discuss the relevant strategy for optimizing stem cell-based gene therapy and discuss the potential strategies for its future application. Keywords: Embryonic stem cell, gene therapy, stem cell, ischemic stroke, mesenchymal stem cell, neural stem cell

Gene and Cell Therapy Funding Opportunities in Horizon 2020: An Overview for 2014–2015

Development of a Web Course on Gene Therapy by the International Consortium of Gene Therapy

The analysis of genomic distribution of retroviral vectors is a powerful tool to monitor ‘vector-on-host’ effects in gene therapy (GT) trials but also provides crucial information about ‘host-on-vector’ influences based on the target cell genetic and epigenetic state. We had the unique occasion to compare the insertional profile of the same therapeutic moloney murine leukemia virus (MLV) vector in the context of the adenosine deaminase-severe combined immunodeficiency (ADA-SCID) genetic background in two GT trials based on infusions of transduced mature lymphocytes (peripheral blood lymphocytes, PBL) or a single infusion of haematopoietic stem/progenitor cells (HSC). We found that vector insertions are cell-specific according to the differential expression profile of target cells, favouring, in PBL-GT, genes involved in immune system and T-cell functions/pathways as well as T-cell DNase hypersensitive sites, differently from HSC-GT. Chromatin conformations and histone modifications influenced integration preferences but we discovered that only H3K27me3 was cell-specifically disfavoured, thus representing a key epigenetic determinant of cell-type dependent insertion distribution. Our study shows that MLV vector insertional profile is cell-specific according to the genetic/chromatin state of the target cell both in vitro and in vivo in patients several years after GT.

176. Novel Molecules That Enhance Adenovirus Transduction of the Airway Epithelium: Reinvigorating Adenovirus-Mediated Gene Therapy

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated enzyme-CAS holds great promise for treating many uncured human diseases and illnesses by precisely correcting harmful point mutations and disrupting disease-causing genes. The recent Food and Drug Association (FDA) approval of the first CRISPR-based gene therapy for sickle cell anemia marks the beginning of a new era in gene editing. However, delivering CRISPR specifically into diseased cells in vivo is a significant challenge and an area of intense research. The identification of new CRISPR/Cas variants, particularly ultra-compact CAS systems with robust gene editing activities, paves the way for the low-capacity delivery vectors to be used in gene therapies. CRISPR/Cas technology has evolved beyond editing DNA to cover a wide spectrum of functionalities, including RNA targeting, disease diagnosis, transcriptional/epigenetic regulation, chromatin imaging, high-throughput screening, and new disease modeling. CRISPR/Cas can be used to engineer B-cells to produce potent antibodies for more effective vaccines and enhance CAR T-cells for the more precise and efficient targeting of tumor cells. However, CRISPR/Cas technology has challenges, including off-target effects, toxicity, immune responses, and inadequate tissue-specific delivery. Overcoming these challenges necessitates the development of a more effective and specific CRISPR/Cas delivery system. This entails strategically utilizing specific gRNAs in conjunction with robust CRISPR/Cas variants to mitigate off-target effects. This review seeks to delve into the intricacies of the CRISPR/Cas mechanism, explore progress in gene therapies, evaluate gene delivery systems, highlight limitations, outline necessary precautions, and scrutinize the ethical considerations associated with its application.

The development of viral vectors and recombinant DNA technology since the 1960s has enabled gene therapy to become a real therapeutic option for several inherited and acquired diseases. After several ups and downs in the gene therapy field, we are currently living a new era in the history of medicine in which several ex vivo and in vivo gene therapies have reached maturity. This is testified by the recent marketing authorization of several gene therapy medicinal products. In addition, many others are currently under evaluation after exhaustive investigation in human clinical trials. In this review, we summarize some of the most significant milestones in the development of gene therapy medicinal products that have already facilitated the treatment of a significant number of rare diseases. Despite progresses in the gene therapy field, the transfer of these innovative therapies to clinical practice is also finding important restrictions. Advances and also challenges in the progress of gene therapy for rare diseases are discussed in this opening review of a Human Gene Therapy issue dedicated to the 30th annual Congress of the European Society for Gene and Cell Therapy.

Background: Current gene-based strategies for treatment of erectile dysfunction (ED) are based on the nitric oxide (NO)/cGMP system; although growth factors, calcium sensitization, and potassium channel expression have been studied. Initial investigations of stem-cell-based therapy have attracted attention. Results of the first gene transfer clinical trial for treatment of ED with maxi-K channels are positive. Moreover, there is progress in gene and stem-cell therapy for the treatment of cardiovascular (CV) diseases. Objective: To improve understanding of gene and stem-cell therapy for CV disease, with emphasis on ED. Methods: Review of current literature. Results/conclusion: Treatment and prevention of ED can be improved by the application of CVD gene/cell-based therapy. New discoveries based on gene- and cell-based therapy will lead to new advances in the treatment of ED.

CHAPTER 15 - Cancer gene therapies progress in pre and postgenomics era

Gene therapy involves the manipulation of genetic material to replace defective or deficient proteins to restore function in disease states. These genes are introduced into cells by mechanical, chemical, and biological approaches. To date, cell-based gene therapy has been hampered by the lack of an abundant, safe, and immunologically acceptable source of tissue. As an alternative, transgenic animals designed to produce therapeutic proteins could overcome some of the issues facing gene therapy but the problem of immune rejection of the tissue remains. This article reports on recently published work indicating the potential to use transgenic Sertoli cells surviving in an allogeneic host by virtue of their ability to create a locally immunoprivileged environment, thereby providing for the continued delivery of a therapeutic protein to the systemic circulation.

BackgroundHemophilia B is an X-linked bleeding disorder caused by a mutation in the gene responsible for encoding coagulation factor IX (FIX). Gene therapy offers promising potential for curing this disease. However, the current method of relatively high dosage of virus injection carries inherent risks. The purpose of this study was to introduce a novel scAAV-DJ/8-LP1-hFIXco vector transduced human umbilical cord blood derived mesenchymal stem cells (HUCMSCs) as an alternative cell-based gene therapy to conventional gene therapy for Hemophilia B.MethodsThe LP1-hFIXco gene structure was designed by us through searching the literature from NCBI and the scAAV-DJ/8-LP1-hFIXco vector was constructed by a commercial company. The HUCMSCs were cultivated in routine approach and transduced with scAAV-DJ/8-LP1-hFIXco vector. The human FIX activation system was employed for detection of hFIXco activity. The RNA and protein expression levels of the hFIXco were evaluated using PCR and western blot techniques. In animal studies, both NSG and F9-KO mice were used for the experiment, in which clotting time was utilized as a parameter for bleeding assessment. The immunohistochemical analysis was used to assess the distribution of HUCMSCs in mouse tissue sections. The safety for tumorigenicity of this cell-based gene therapy was evaluated by pathological observation after hematoxylin-eosin staining.ResultsThe transduction of HUCMSCs with the scAAV-DJ/8-LP1-hFIXco vector results in consistent and sustainable secretion of human FIXco during 5 months period both in vitro and in mouse model. The secretion level (hFIXco activity: 97.1 ± 2.3% at day 7 to 48.8 ± 4.5% at 5 months) was comparable to that observed following intravenous injection with a high dose of the viral vector (hFIXco activity: 95.2 ± 2.2% to 40.8 ± 4.3%). After a 5-month observation period, no clonal expansions of the transduced cells in tissues were observed in any of the mice studied.ConclusionsWe have discovered a novel and safer HUCMSCs mediated approach potentially effective for gene therapy in hemophilia B.

Expanded Opportunities for Methods and Clinical Development